The encapsulation of water-insoluble solids can be achieved by physical, physico-chemical, or chemical processes. Physical processes, such as spray-drying, fluidized bed coating or supercritical fluid spray coating all subject the material to be dried at above room temperature conditions, which can degrade thermolabile compounds (1). Therefore, physico-chemical processes, such as coacervation, or chemical processes, such as interfacial polymerization or enzymatic cross-linking, are microencapsulation alternatives that maintain the chemical integrity of the compounds to be encapsulated (2). The physico-chemical microencapsulation processes used to encapsulate insoluble solids usually employ methods based on ionic interactions, such as ionic gelation, acid precipitation, coacervation and layer-by-layer processes (2). These processes employ charged macromolecules, such as proteins, polysaccharides or synthetic polyelectrolites that interact electrostatically with other macromolecules or oppositely charged ions in the solution or on the surface of the solid to be encapsulated. Thus, a polymeric complex matrix gel that coats the solid of interest is generated. Microencapsulation by means of ionic gelation has advantages over the other methods based in ionic interactions, because it only uses one charged macromolecule, thereby simplifying the system and the costs of the process, as well as allowing greater control over the viscosity of the work system. Ionic gelation consists of the extrusion or emulsification of a charged macromolecule (e.g. sodium alginate) incorporated into drops, in a counter ion (e.g. calcium chloride) solution, leading to the immediate gelation of the exterior of the drop upon contact.
After that, the counter ions continue their diffusion toward the particle's interior and cause its complete gelation. However, the diffusion mechanism of the counter ion usually causes a heterogeneous gelation of the particle, which is not convenient for applications wherein the release kinetics of an active compound must be controlled (3). Ionic gelation through an internal gelation mechanism solves the drawback of diffusion gelation by employing an inactive form of the counter ion that is activated (e.g. by a change in pH) only after it is mixed with the macromolecule (3).
This ionic gelation method has been applied to the encapsulation of polyphenols (2), osteoporosis medications (4), probiotics (5, 6), antibiotics (7) and for generating biocompatible capsules of active compounds (8). However, one of the main inconveniences is the high porosity of the matrix-forming gel of the microcapsule, which allows a quick diffusion of the encapsulated compounds (9-11). This issue can be solved by generating a gel matrix based on proteins or a mix of proteins and polysaccharides through heating, enzymatic cross-linking, or acidification (1). Obtaining a gel matrix of the microparticle by heating (12) or acidification may not be viable for compounds that are sensitive to those environmental conditions, and in the case of cross-linking, its usage possibilities and cross-linking effectiveness are determined by the type of protein used, thereby limiting its range of applications. The prior art of the microencapsulation process by ionic gelation shows the need to generate a low-porosity gel matrix for the microparticle, based on proteins or a mix of proteins and polysaccharides, under conditions that do not include excessive heating nor acidification of the medium in its production.
The present invention, through a microencapsulation process, is able to achieve the formation of a matrix of charged macromolecules on the surface of water-insoluble solids, generating microspheres by controlled adsorption of the macromolecules to the surface of the solid in the presence of polyvalent ions at low temperature and its gelation by increasing the temperature to room temperature or higher, depending on the type of macromolecule being used.